Methyl ferulic acid exerts anti-apoptotic effects on L-02 cells via the ROS-mediated signaling pathway

Abstract

The present study aimed to investigate the anti-apoptotic effects of methyl ferulic acid (MFA) on L-02 cell apoptosis induced by ethanol, and to elucidate the possible underlying mechanisms. L-02 cells were examined after being soaked in ethanol (400 mM) to allow the ethanol to permeate into the cells for 24 h. Cell survival was measured by MTT assay. Cell apoptosis was assessed by both flow cytometry and single-stranded DNA assays. Intracellular reactive oxygen species (ROS) production was determined using the 2',7'-dichlorofluorescein-diacetate dye. The protein expression levels of p38, p-p38, JNK, p-JNK, NADPH oxidase 4 (NOX4), p22, Bax and Bcl-2 were measured by western blot analysis. The mRNA expression levels of NOX4 and p22 were measured by RT-PCR. It was identified that MFA markedly suppressed the ethanol-induced apoptosis and necrosis of L-02 cells. In addition, MFA decreased the expression levels of superoxide dismutase, catalase and phospholipid hydroperoxide gluthione peroxidase, and downregulated the levels of Bax/Bcl-2 and the cleaved forms of caspase-3 in a dose- and time-dependent manner. This indicated that MFA attenuated the apoptosis of L-02 cells. MFA also decreased the elevated mRNA and protein expression levels of Nox4 and p22phox, and the production of intracellular ROS triggered by ethanol. Further analysis demonstrated that MFA significantly attenuated the phosphorylation of JNK and p38, which are major components of the mitogen-activated protein kinase (MAPK) pathways. On the whole, the findings of this study demonstrated that MFA attenuated the apoptotic cell death of L-02 cells by reducing the generation of ROS and inactivating the MAPK pathways.

Ferulic acid influences Nrf2 activation to restore testicular tissue from cadmium‐induced oxidative challenge, inflammation, and apoptosis in rats

“…In line with our findings, a previous study found that low doses of FA has antiapoptotic effect mediated via upregulating of sirtuins proteins in PC12 cells (Moghadam et al, 2018). Similarly, it has been reported that FA derivative attenuated ethanol-induced apoptosis in cell line by inhibiting ROS and MAPK signaling pathways (Li et al, 2018).…”

“…In line with our findings, a previous study found that low doses of FA has antiapoptotic effect mediated via upregulating of sirtuins proteins in PC12 cells (Moghadam et al., 2018). Similarly, it has been reported that FA derivative attenuated ethanol‐induced apoptosis in cell line by inhibiting ROS and MAPK signaling pathways (Li et al., 2018). Furthermore, FA was reported to protect cortical neurons against glutamate‐induced apoptosis by upregulating Bcl‐2, antiapoptotic marker, mediated by activation of PI3K/Akt as well as enhancement of MEK/ERK signaling pathway that hinder caspase activation and preventing mitochondrial release of cytochrome c (Jin et al., 2007).…”

miR-378b Regulates Insulin Sensitivity by Targeting Insulin Receptor and p110α in Alcohol-Induced Hepatic Steatosis

“…Numerous studies have shown that alcohol can cause alcoholic liver damage by activating oxidative stress, inhibiting liver fat-acid metabolism, and increasing liver lipid synthesis (Li et al, 2017;Li et al, 2018;Yang C. F. et al, 2018). Studies have also revealed that alcohol reduces hepatic glycogen synthesis and increases gluconeogenesis by regulating the liver insulin signaling pathway (Pang et al, 2009;Magdaleno et al, 2017).…”

Ethanol-Induced Hepatic Insulin Resistance is Ameliorated by Methyl Ferulic Acid Through the PI3K/AKT Signaling Pathway

“…Hence, Chinese herbal medicine for the prevention and treatment of insulin resistance has become a research hotspot domestically and overseas. Methyl ferulic acid (MFA) is a white needle compound that possesses a variety of pharmacological properties, including antioxidant stress, anti-apoptosis, and anti-inflammatory effects (Li et al, 2017; Cheng et al, 2018; Li et al, 2018; Yang et al, 2018; Cheng et al, 2019). However, to our knowledge, there are still no reports concerning the effect of MFA on insulin resistance at home and abroad.…”